The objective of this research proposal is to investigate the mechanism of reticuloendothelial system (RES) failure during hemorrhagic shock with emphasis on dysfunction of the opsonic system in the etiology of RE depression. The functional state of the RES is critical in terms of the ability of an animal to survive severe shock. Moreover, the physiologic state of the RES especially with respect to phagocytosis is highly dependent on opsonic protein. These findings, coupled with our preliminary data suggest a new mechanism to explain the etiology of RE host defense failure during hemorrhagic shock. This mechanism suggests that the failure of the RES is due to a depletion of the plasma opsonin levels. Additionally, since opsonin depletion exists following major surgery, burn injury, and traumatic shock, all these forms of injury may have a common pathway with respect to RE failure mediated by a lack of this humoral factor. The central role of the RES in host defense during shock suggests that failure of this system would decrease the ability of the host to clear blood-borne effete cells, denatured protein, bacteria, endotoxins, lysosomal enzymes, and other complexes released into the circulation during hemorrhage. Opsonic protein or "recognition factor" is an alpha-2-acid glycoprotein of large molecular weight which can be isolated with a high degree of purification. The availability of this purified protein provides a means to evaluate opsonin therapy as an approach to circumvent RE failure during experimental shock and to correlate RES functional ability with survival. Additionally, antibodies made against purified opsonic protein provide us with a unique immunologic method to manipulate the RES. Thus, one can effectively stimulate or depress the RES, and clearly dissect out the role of the RES in shock resistance. This inter-disciplinary research project between the departments of physiology and surgery will attempt to bring together individuals with different areas of expertise to focus on the mechanism of RES failure during shock, with applicability of this basic information to the clinical setting.